• Optic atrophy refers to the degeneration of retinal ganglion axons of the optic nerve and a resulting picture of a pale optic nerve on fundoscopy.
• It is a sign indicative of chronic optic nerve insult rather than a distinct disease entity.

Unilateral/bilateral optic atrophy

• Optic atrophy is identified weeks to months after an initial insult such as optic neuritis, trauma, or ischemia. May occur insidiously with no acute inciting event in more genetic or toxic causes. Frequently, it is noted by the physician during a routine eye exam.
• Asymmetry of disc color is often first subtle finding.
• Temporal part of optic disc is pale initially; later, the entire disc becomes pale/white.
• Optic disc pallor (Fig. E1) occurs 4 to 6 wk after optic nerve insult.
• Unilateral lesion produces a relative afferent pupillary defect (RAPD): When swinging flashlight eye to eye, the abnormal pupil dilates to direct light.
• Decreased visual acuity, blurred vision, visual field deficits (e.g., central scotoma), abnormal color vision (e.g., red desaturation).

• Inflammatory optic neuritis: MS, sarcoidosis, neuromyelitis spectrum disorder, infections (syphilis, CMV, HIV, Lyme disease, cat-scratch disease)
• Vascular: Arteritic and nonarteritic ischemic optic neuropathy, central retinal artery occlusion, temporal arteritis, diabetes
• Compression: Pituitary, orbital, or other tumors, idiopathic intracranial hypertension, meningioma, thyroid eye disease
• Hereditary: Leber hereditary optic neuropathy, autosomal dominant optic atrophy, leukodystrophies, other mitochondrial diseases.
• Nutritional, toxic, and metabolic: Amiodarone, isoniazid, tacrolimus, ethambutol, linezolid, vigabatrin, B₁₂ deficiency, folate deficiency, copper deficiency, methanol, tobacco, alcohol¹
• Trauma
• Radiation
• Glaucoma (end-stage disease)

Optic disc anomalies such as myelinated nerve fibers, “blonde” fundus

• A detailed history to identify onset and course, exposure to risk factors such as toxic/nutritional factors, detailed family history, and associated findings such as headache, eye pain, proptosis, or neurologic deficits.
• Ophthalmic examination to document deficits of visual acuity, color vision, contrast sensitivity, and visual fields must be performed. Relative afferent pupillary defect (RAPD) on swinging flashlight examination is sine qua non for unilateral optic nerve disease and must be documented. Absence indicates retinal disease or bilateral lesions.
• General examination and neurologic examination can provide clues to an underlying cause.

• Serum B₁₂, RPR, HIV
• Autoimmune diseases: ESR, ANA, ACE, aquaporin-4 antibodies (NMO IgG)
• Lumbar puncture if unknown cause or other associated neurologic deficits

• Visual field testing can help characterize and localize the etiology.
• Optical coherence tomography (OCT) to assess the thickness of the peripapillary retinal nerve fiber layer to establish and monitor.
• MRI of the brain and orbits with contrast, fat suppression, and special (thin) cuts through orbits is necessary to identify compressive lesions in all patients with unexplained optic atrophy; especially important in patients with positive predictive factors for abnormal imaging (e.g., young age, progression, bilateral findings).²
• If sarcoid is suspected, order chest X-ray and/or chest CT.

Treat the underlying cause-discontinue identifiable toxins, use B₁₂ replacement, neurosurgical intervention is necessary if tumor is found; consider IV steroids if there is evidence for active demyelinating disease.

The optic nerve does not regenerate, although symptoms often improve, especially if the provoking cause is removed.

• Visual loss usually occurs over weeks to months.

Ophthalmologist

Neurologist depending on the etiology

• An experienced clinician should be able to identify pale optic discs and an RAPD.
• Pupillary dilation with mydriatic agents (e.g., tropicamide) may be necessary to optimize funduscopic examination.
• Patient education material can be obtained from the National Eye Institute, Department of Health and Human Services, 9000 Rockville Pike, Bethesda, MD 20814.